Efficacy of Sirolimus Treatment in PEComa–10 Years of Practice Perspective

Abstract

Perivascular epithelioid cell tumors (PEComa) represent a family of rare mesenchymal tumors resultant from deregulation in mTOR pathway activity. The aim of this study is to evaluate the long-term efficacy of targeted PEComa treatment. We reviewed all consecutive patients with PEComa who started systemic treatment with sirolimus in our reference sarcoma center between January 2011 and August 2020. Histopathology of PEComa was reviewed and confirmed in all cases by a designated sarcoma pathologist. Any surviving progression-free patients were censored at the last follow-up (31 March 2021). Survival curves were calculated according to Kaplan–Meier method and compared with the log-rank test or a Cox proportional hazard model. Fifteen (12 females and 3 males) consecutive PEComa patients were treated. The median age of patients treated systemically was 50 years. Median progression-free survival (PFS) was 4.9 months (95% CI: 3.8-NA) for first-line chemotherapy and was not reached (95% CI: 42.0-NA) for sirolimus as first-line therapy. There was one objective response (OR) in the chemotherapy group. The OR rate reached 73% (11/15 cases) for sirolimus regardless of the treatment line. All patients archived disease control. Three patients died due to disease progression after 55, 32, and 32 months since metastatic disease diagnosis. After a median follow-up of 55.7 (range: 3.2–220) months, the 5 yr OS was 65% (CI 95% 39–100). Our study is the largest single-institution report on PEComa systemic targeted therapy and fills the gap in the field of advanced PEComa care since the FDA/EMEA approval of sirolimus.

Insights into clinical diagnosis and treatment of malignant hepatic perivascular epithelioid cell tumor

“…Ultrasonography of the abdomen usually shows hyperechogenic cystic solid lesions with abundant blood supply. These tumors are hypodense to isodense on CT. MRI shows hypointense to isointense in comparison to skeletal muscle on T1-weighted imaging, and these tumors are heterogeneously hyperintense on T2weighted imaging (1,4). Due to abundant vascularization from hepatic artery branches, we can observe that the lesion is strongly and heterogeneously enhanced in ultrasonography involving intravenous contrast media.…”

Spectrum of Presentations and Management Strategies in Renal Angiomyolipoma

“…Chemotherapy (anthracycline and gemcitabine-based regimens) and antiangiogenic treatments would be reasonable options for subsequent lines of treatment. Another study analyzed 15 consecutive patients with PEComa, who received sirolimus up-front (11 patients) or received doxorubicin-based chemotherapy in the front-line and sirolimus in subsequent lines (four patients) ( 35 ). The ORR was 73% in the sirolimus arm, while only one patient had a response in the chemotherapy arm.…”

Dermatologic Disease-Directed Targeted Therapy (D3T2): The Application of Biomarker-Based Precision Medicine for the Personalized Treatment of Skin Conditions—Precision Dermatology

“…On November 23, 2021, the FDA approved the mTOR inhibitor nab-sirolimus (nanoparticle albumin-bound sirolimus) for the treatment of PEComas [99,103]. The mTOR pathway is activated by alterations in a variety of genes, including TSC1 and TSC2; PEComa patients with a genomic aberration of TSC2 may respond better to sirolimus-type therapy than those with a gene abnormality of TSC1 [97,104]. In…”